Patient SE translation (SET) is a carcinogen in facilitating cellular growth and proliferation, and promoting tumorigenesis and metastasis. The present study was to investigate the resistance mechanisms associated with SET in paclitaxel-induced human breast cancer cells. The different expressions of SET, ATP-binding cassette (ABC) transporters and PI3K/Akt pathway between paclitaxel sensitive MCF-7/S and paclitaxel resistant MCF-7/PTX cells were identified using western blotting. We adopted plasmid transfection to upregulate SET in MCF-7/S cells and a novel SET antagonist COG112 to decrease SET in MCF-7/PTX cells. Subsequently, cell viability to paclitaxel was assessed by MTT assay and cell apoptosis was analyzed by flow cytometry. We found that levels of SET, ABC transporters and PI3K/Akt pathway were elevated in MCF-7/PTX. Upregulation of SET in MCF-7/S cells expressed resistant to paclitaxel and decreased cell apoptosis. Moreover, overexpression of SET promoted the mRNA and protein level of ABC transporters and PI3K/Akt signal pathway in MCF-7/S cells. Conversely, decreased level of SET by COG112 not only significantly sensitized MCF-7/PTX cells to paclitaxel, but also enhanced paclitaxel-induced cell apoptosis. Additionally, the levels of the ABC transporters and PI3K/Akt signal pathway were also reduced in the COG112-treated MCF-7/PTX cells. The above results demonstrated that SET was associated with paclitaxel resistance in MCF-7/PTX cells.

Elderly patients with non-small-cell lung cancer (NSCLC) exhibit worse reactions to anticancer treatments. Adenocarcinoma (AC) is the predominant histologic subtype of NSCLC, is diverse and heterogeneous, and shows different outcomes and responses to treatment. The aim of this study was to establish a nomogram that includes the important prognostic factors based on the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. We collected 53,694 patients of older than 60 who have been diagnosed with lung AC from the SEER database. Univariate and multivariate Cox regression analyses were used to screen the independent prognostic factors, which were used to construct a nomogram for predicting survival rates in elderly AC patients. The nomogram was evaluated using the concordance index (C-index), calibration curves, net reclassification index (NRI), integrated discrimination improvement (IDI), and decision-curve analysis (DCA). Elderly AC patients were randomly divided into a training cohort and validation cohort. The nomogram model included the following 11 prognostic factors: age, sex, race, marital status, tumor site, histologic grade, American Joint Committee for Cancer (AJCC) stage, surgery status, radiotherapy status, chemotherapy status, and insurance type. The C-indexes of the training and validation cohorts for cancer-specific survival (CSS) (0.832 and 0.832, respectively) based on the nomogram model were higher than those of the AJCC model (0.777 and 0.774, respectively). The CSS discrimination performance as indicated by the AUC was better in the nomogram model than the AJCC model at 1, 3, and 5 years in both the training cohort (0.888 vs. 0.833, 0.887 vs. 0.837, and 0.876 vs. 0.830, respectively) and the validation cohort (0.890 vs. 0.832, 0.883 vs. 0.834, and 0.880 vs. 0.831, respectively). The predicted CSS probabilities showed optimal agreement with the actual observations in nomogram calibration plots. The NRI, IDI, and DCA for the 1-, 3-, and 5-year follow-up examinations verified the clinical usability and practical decision-making effects of the new model. We have developed a reliable nomogram for determining the prognosis of elderly AC patients, which demonstrated excellent discrimination and clinical usability and more accurate prognosis predictions. The nomogram may improve clinical decision-making and prognosis predictions for elderly AC patients.

Non-small cell lung cancer remains the most common malignant cancer. We identified 43140 advanced NSCLC patients from the SEER database to develop and validate a new prognostic model. The prognostic performance was evaluated by P value, concordance index, net reclassification index, integrated discrimination improvement, and decision curve analysis. The following variables were contained in the final prognostic model: age, sex, race, TNM stage, and grade and treatment options. Compared to the AJCC staging system, this prognostic model is conducive to the implementation of individualized clinical treatment schemes and can be an important part in the precise medical care of NSCLC tumors.

There are few reports on the distribution of the plasma trough concentration (C_min ) of teicoplanin in patients with augmented renal clearance (ARC) and on the safety of a high-dose regimen (HD; 800 mg loading dose for q12h three times followed by an 800 mg qd maintenance dose). The objective of this study was to determine the C_min values of teicoplanin in ARC patients using HD teicoplanin to provide a reference for individualized medication. Data on patients treated with teicoplanin from January 2019 to January 2021 were collected retrospectively and divided into ARC (creatinine clearance rate [CCr] >130 ml/min, n = 22) and non-ARC (60 ml/min ≤ CCr ≤130 ml/min, n = 24) groups. The C_min values in the two patient groups were analysed during the HD and the low-dose regimen (LD; all other regimens) on the third day of medication and during the dose maintenance period. Liver and kidney function indexes were also analysed before and after medication. On the third day of the HD, C_min did not differ significantly between the ARC and non-ARC groups (17.3 ± 9.2 mg/L [mean ± SD] vs. 15.5 ± 7.9 mg/L, p = 0.663), while C_min in the ARC group was significantly lower for the LD (6.8 ± 3.9 mg/L, p = 0.039). During the dose maintenance period, C_min in the ARC group when receiving the HD (18.3 ± 5.1 mg/L) was significantly lower than that in the non-ARC group (25.5 ± 11.9 mg/L, p = 0.016) and significantly higher than that for the LD (12.2 ± 6.3 mg/L, p = 0.022). Nephrotoxicity and hepatotoxicity incidence rates did not differ significantly between these groups. These results suggest that it is necessary to apply a loading dose of 800 mg (but not higher) q12h three times for patients with ARC, with 800 mg needed as a maintenance dose during severe infection, and 600 mg or 400 mg for mild infection.

The occurrence of chemoresistance greatly restricts the efficacy of antitumor drugs, and so novel agents are urgently needed to abrogate resistant phenotypes. In this study we investigated the role of patient SE translation (SET) in the human breast cancer paclitaxel-resistant cell line (MCF-7/PTX) and the underlying reversal mechanism of FA18, a new synthetic histone deacetylase inhibitor. The expressions of SET, protein phosphatase 2A (PP2A), and factors related to the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and downstream mitochondrial apoptosis pathways were determined in MCF-7/PTX cells. In order to explore the role of SET in inducing drug resistance, a SET antagonist OP449 was used to down-regulate SET in MCF-7/PTX cells, and the cell viability, cell apoptosis, and pathway-related factors were assessed. Furthermore, the reversal effects of FA18 and its underlying mechanisms were investigated in vitro and in vivo. We found that SET and the PI3K/Akt signaling pathway were activated in MCF-7/PTX cells. The down-regulation of SET by OP449 significantly sensitized MCF-7/PTX cells to paclitaxel (PTX) and induced cell apoptosis. In addition, SET-induced PTX resistance was associated with activation of the PI3K/Akt signaling pathway and inhibition of mitochondrial apoptosis pathways. FA18 significantly reduced the mRNA and protein levels of SET in MCF-7/PTX cells. Furthermore, FA18 significantly inhibited SET-mediated resistance by attenuating the PI3K/Akt signaling pathway and activating mitochondrial apoptosis pathways. Additionally, FA18 significantly reduced the SET level via the PI3K/Akt signaling pathway both in vitro and in vivo. These results suggest that the overexpression of SET is associated with drug resistance in MCF-7/PTX cells. FA18 reversed this drug resistance, possibly via suppression of the SET/PI3K/Akt signaling pathway.

Expression of concern for ‘HDACI regulates the PI3K/Akt signaling pathway to reverse MCF-7/PTX resistance by inhibiting SET’ by Weipeng Zhang et al., RSC Adv., 2016, 6, 48072–48082, https://doi.org/10.1039/C6RA06423J